Book of Abstracts: Albany 2009

Organization, processing, and repair of genetic material involves direct interactions between DNA double helices at small distances. These interactions are believed to be independent of the base pair sequence because the nucleotides are buried inside the double helix and shielded by the charged sugar-phosphate backbone. A recent theory challenged this concept, predicting that DNA-DNA interactions depend on the backbone structure and that the sequence dependence of the backbone structure may be sufficiently strong to affect the interactions. However, the latter hypothesis has not been experimentally verified. Here we demonstrate sequence homology recognition between duplex DNAs without unzipping of the double helix and without proteins or other ligands. We imaged a mixture of two fluorescently tagged DNAs with identical nucleotide composition and length, but different sequences. Their segregation within liquid crystalline spherulites reveals not only the recognition without any single-strand fragments but also the recognition between duplexes separated by more than a nanometre of water. Although cells tightly regulate interactions between DNA through a variety of proteins, the underlying DNA-DNA forces may still be utilized in some form for the observed pairing of homologous duplexes. The ability of these forces to recognize only large-scale (> 50-100 bp) sequence homology may be crucial and it may not be a coincidence that it matches the minimal 50-100 bp homology requirement essential for avoiding mistakes in genetic recombination.

1Division of Molecular Biosciences
Imperial College London
SW7 2AZ London, UK2Department of Chemistry
Imperial College London
SW7 2AZ London, UK3Section on Physical Biochemistry
National Institute of Child Health and Human Development
National Institutes of Health, DHHS
Bethesda, MD 20892, USA